Apparatus comprising an ion mobility spectrometer

ABSTRACT

A mass spectrometer is disclosed comprising a first chamber ( 10 ) and a second chamber ( 5 ). The second chamber ( 5 ) is located downstream of the first chamber  10  and an inter-chamber aperture ( 12 ) is provided between the two chambers ( 5,10 ). An ion guide ( 13 ) is located in the first chamber ( 10 ) and an ion mobility spectrometer ( 6 ) is located in the second chamber ( 5 ). Helium gas is provided to the first chamber ( 10 ). As ions are accelerated towards the ion mobility spectrometer  6  from a relatively low pressure region they pass initially into the first chamber ( 10 ). The helium gas provided in the first chamber ( 10 ) minimises ion fragmentation and ion discrimination effects as ions are accelerated into a relatively high pressure region. The ions are then transmitted by the ion guide ( 13 ) and are subsequently transmitted to the ion mobility spectrometer ( 6 ) located in the second chamber ( 5 ).

The present invention relates to apparatus comprising an ion mobilityspectrometer, a mass spectrometer, a method of ion mobility spectrometryand a method of mass spectrometry.

Ion mobility spectrometers (“IMS”) are known which are provided atsub-ambient pressure conditions within the vacuum chamber of a massspectrometer. Typically, the chamber housing the ion mobilityspectrometer is maintained at a gas pressure in the range of 0.1 to 10mbar. The chamber housing the ion mobility spectrometer must be providedin a differentially pumped vacuum chamber in order to minimise gasloading of a mass analyser which is arranged downstream of the ionmobility spectrometer in a separate vacuum chamber. Depending upon thelocation of the ion mobility spectrometer in the overall massspectrometer, ions may have passed through a region of relatively lowpressure prior to entry into the chamber housing the ion mobilityspectrometer. If ions pass through a region of relatively low pressureimmediately prior to the chamber housing the ion mobility spectrometerthen it is necessary to drive the ions into the chamber housing the ionmobility spectrometer against a significant outflow of gas from thechamber. The requirement to drive ions into the chamber housing the ionmobility spectrometer against a significant outflow of gas can beparticularly problematic especially if some of the ions are relativelyfragile or have relatively low mobilities since the use of a relativelyhigh electric field to drive the ions into the relatively high pressurechamber can lead to undesired effects such as ion fragmentation and/orion mobility effects.

It is therefore desired to provide an improved apparatus comprising anion mobility spectrometer.

According to an aspect of the present invention there is providedapparatus comprising:

a first chamber;

a second chamber located downstream of the first chamber;

an ion mobility spectrometer or separator located in the second chamber;

a device for providing a first gas or mixture of gases to the firstchamber, the first gas or mixture of gases having a first averagedensity or molecular weight M₁; and

a device for providing a second gas or mixture of gases to the secondchamber, the second gas or mixture of gases having a second averagedensity or molecular weight M₂, wherein M₁<M₂.

The ratio M₂/M₁ is preferably selected from the group consisting of: (i)≧1.1; (ii) ≧1.5; (iii) ≧2.0; (iv) ≧3.0; (v) ≧4.0; (vi) ≧5.0; (vii) ≧6.0;(viii) ≧7.0; (ix) ≧8.0; (x) ≧9.0; (xi) ≧10.0; (xii) ≧11.0; (xiii) ≧12.0;(xiv) ≧13.0; (xv) ≧14.0; (xvi) ≧15.0; (xvii) ≧16.0; (xviii) ≧17.0; (xix)≧18.0; (xx) ≧19.0; (xxi) ≧20.0; (xxii) ≧25.0; (xxiii) ≧30.0; (xxiv)≧35.0; (xxv) ≧40.0; (xxvi) ≧45.0; (xxvii) ≧50.0; (xxviii) ≧55.0; (xxix)≧60.0; (xxx) ≧65.0; and (xxxi) ≧70.0. According to an embodiment theratio M₂/M₁ may be selected from the group consisting of: (i) 1-2; (ii)2-3; (iii) 3-4; (iv) 4-5; (v) 5-6; (vi) 6-7; (vii) 7-8; (viii) 8-9; (ix)9-10; (x) 10-11; (xi) 11-12; (xii) 12-13; (xiii) 13-14; (xiv) 14-15;(xv) 15-16; (xvi) 16-17; (xvii) 17-18; (xviii) 18-19; (xix) 19-20; (xx)20-25; (xxi) 25-30; (xxii) 30-35; (xxiii) 35-40; (xxiv) 40-45; (xxv)45-50; (xxvi) 50-55; (xxvii) 55-60; (xxviii) 60-65; (xxix) 65-70; and(xxx) ≧70.

The first chamber preferably comprises a housing having an ion inletaperture and a first gas outlet. The apparatus preferably furthercomprises an inter-chamber aperture between the first chamber and thesecond chamber.

The first gas or mixture of gases preferably comprises one or more gasesselected from the group consisting of: (i) helium; (ii) hydrogen; (iii)neon; (iv) methane; (v) ammonia; (vi) nitrogen; (vii) argon; (viii)xenon; (ix) air; and (x) SF6 or sulphur hexafluoride.

According to an embodiment the first gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% helium.

According to an embodiment the first gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% hydrogen.

According to an embodiment the first gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% neon.

According to an embodiment the first gas or mixture of gases comprisesat least 5%i 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% methane.

According to an embodiment the first gas or mixture of gases comprisesat least 5%, .10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%,65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% ammonia.

According to an embodiment the first gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% nitrogen.

According to an embodiment the first gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% argon.

According to an embodiment the first gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% xenon.

According to an embodiment the first gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% air.

According to an embodiment the first gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% SF6 or sulphur hexafluoride.

The first gas or mixture of gases is preferably provided at a pressureselected from the group consisting of: (i) <0.1 mbar; (ii) ≧0.1 mbar;(iii) ≧0.2 mbar; (iv) ≧0.3 mbar; (v) ≧0.4 mbar; (vi) ≧0.5 mbar; (vii)≧0.6 mbar; (viii) ≧0.7 mbar; (ix) ≧0.8 mbar; (x) ≧0.9 mbar; (xi) ≧1.0mbar; (xii) ≧1.1 mbar; (xiii) ≧1.2 mbar; (xiv) ≧1.3 mbar; (xv) ≧1.4mbar; (xvi) ≧1.5 mbar; (xvii) ≧1.6 mbar; (xviii) ≧1.7 mbar; (xix) ≧1.8mbar; (xx) ≧1.9 mbar; (xxi) ≧2.0 mbar; (xxii) ≧3.0 mbar; (xxiii) ≧4.0mbar; (xxiv) ≧5.0 mbar; (xxv) ≧6.0 mbar; (xxvi) ≧7.0 mbar; (xxvii) ≧8.0mbar; (xxviii) ≧9.0 mbar; and (xxix) ≧10.0 mbar. The first gas ormixture of gases is preferably provided at a pressure selected from thegroup consisting of: (i) 0.1-0.5 mbar; (ii) 0.5-1.0 mbar; (iii) 1.0-1.5mbar; (iv) 1.5-2.0 mbar; (v) 2.0-2.5 mbar; (vi) 2.5-3.0 mbar; (vii)3.0-3.5 mbar; (viii) 3.5-4.0 mbar; (ix) 4.0-4.5 mbar; (x) 4.5-5.0 mbar;(xi) 5.0-5.5 mbar; (xii) 5.5-6.0 mbar; (xiii) 6.0-6.5 mbar; (xiv)6.5-7.0 mbar; (xv) 7.0-7.5 mbar; (xvi) 7.5-8.0 mbar; (xvii) 8.0-8.5mbar; (xviii) 8.5-9.0 mbar; (xix) 9.0-9.5 mbar; and (xx) 9.5-10.0 mbar.

According to an embodiment the first chamber has a length selected fromthe group consisting of: (i) <20 mm; (ii) 20-40 mm; (iii) 40-60 mm; (iv)60-80 mm; (v) 80-100 mm; (vi) 100-120 mm; (vii) 120-140 mm; (viii)140-160 mm; (ix) 160-180 mm; (x) 180-200 mm; (xi) 200-220 mm; (xii)220-240 mm; (xiii) 240-260 mm; (xiv) 260-280 mm; (xv) 280-300 mm; and(xvi) >300 mm.

The apparatus preferably further comprises a first ion guide comprisinga plurality of electrodes located in the first chamber. The first ionguide preferably has a length selected from the group consisting of: (i)<20 mm; (ii) 20-40 mm; (iii) 40-60 mm; (iv) 60-80 mm; (v) 80-100 mm;(vi) 100-120 mm; (vii) 120-140 mm; (viii) 140-160 mm; (ix) 160-180 mm;(x) 180-200 mm; (xi) 200-220 mm; (xii) 220-240 mm; (xiii) 240-260 mm;(xiv) 260-280 mm; (xv) 280-300 mm; and (xvi) >300 mm.

The first ion guide may comprise:

(i) a multipole rod set or a segmented multipole rod set;

(ii) an ion tunnel or ion funnel; or

(iii) a stack or array of planar, plate or mesh electrodes.

The multipole rod set or the segmented multipole rod set preferablycomprises a quadrupole rod set, a hexapole rod set, an octapole rod setor a rod set comprising more than eight rods.

The ion tunnel or ion funnel preferably comprises a plurality ofelectrodes or at least 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100electrodes having apertures through which ions are transmitted in use,wherein at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the electrodes haveapertures which are of substantially the same size or area or which haveapertures which become progressively larger and/or smaller in size or inarea. At least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the electrodespreferably have internal diameters or dimensions selected from the groupconsisting of: (i) ≦1.0 mm; (ii) ≦2.0 mm; (iii) ≦3.0 mm; (iv) ≦4.0 mm;(v) ≦5.0 mm; (vi) ≦6.0 mm; (vii) ≦7.0 mm; (viii) ≦8.0 mm; (ix) ≦9.0 mm;(x) ≦10.0 mm; and (xi) ≧10.0 mm.

The stack or array of planar, plate or mesh electrodes preferablycomprises a plurality or at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19 or 20 planar, plate or mesh electrodesarranged generally in the plane in which ions travel in use, wherein atleast 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% of the planar, plate or meshelectrodes are arranged generally in the plane in which ions travel inuse. The apparatus preferably further comprises AC or RF voltage meansfor supplying the plurality of planar, plate or mesh electrodes with anAC or RF voltage and wherein adjacent planar, plate or mesh electrodesare supplied with opposite phases of the AC or RF voltage.

The first ion guide preferably comprises a plurality of axial segmentsor at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75,80, 85, 90, 95 or 100 axial segments.

According to an embodiment the apparatus further comprises transient DCvoltage means arranged and adapted to apply one or more transient DCvoltages or potentials or one or more transient DC voltage or potentialwaveforms to electrodes forming the first ion guide in order to urge atleast some ions along at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%,45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of theaxial length of the first ion guide.

According to an embodiment the apparatus further comprises AC or RFvoltage means arranged and adapted to apply two or more phase-shifted ACor RF voltages to the plurality of electrodes forming the first ionguide in order to urge at least some ions along at least 5%, 10%, 15%,20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95% or 100% of the axial length of the first ion guide.

The first ion guide preferably further comprises AC or RF voltage meansarranged and adapted to apply an AC or RF voltage to at least 5%, 10%,15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%,85%, 90%, 95% or 100% of the plurality of electrodes forming the firstion guide in order to confine ions radially within the first ion guide.The AC or RF voltage means is preferably arranged and adapted to supplyan AC or RF voltage to the plurality of electrodes forming the first ionguide having an amplitude selected from the group consisting of: (i) <50V peak to peak; (ii) 50-100 V peak to peak; (iii) 100-150 V peak topeak; (iv) 150-200 V peak to peak; (v) 200-250 V peak to peak; (vi)250-300 V peak to peak; (vii) 300-350 V peak to peak; (viii) 350-400 Vpeak to peak; (ix) 400-450 V peak to peak; (x) 450-500 V peak to peak;and (xi) >500 V peak to peak. The AC or RF voltage means is preferablyarranged and adapted to supply an AC or RF voltage to the plurality ofelectrodes forming the first ion guide having a frequency selected fromthe group consisting of: (i) <100 kHz; (ii) 100-200 kHz; (iii) 200-300kHz; (iv) 300-400 kHz; (v) 400-500 kHz; (vi) 0.5-1.0 MHz; (vii) 1.0-1.5MHz; (viii) 1.5-2.0 MHz; (ix) 2.0-2.5 MHz; (x), 2.5-3.0 MHz; (xi)3.0-3.5 MHz; (xii) 3.5-4.0 MHz; (xiii) 4.0-4.5 MHz; (xiv) 4.5-5.0 MHz;(xv) 5.0-5.5 MHz; (xvi) 5.5-6.0 MHz; (xvii) 6.0-6.5 MHz; (xviii) 6.5-7.0MHz; (xix) 7.0-7.5 MHz; (xx) 7.5-8.0 MHz; (xxi) 8.0-8.5 MHz; (xxii)8.5-9.0 MHz; (xxiii) 9.0-9.5 MHz; (xxiv) 9.5-10.0 MHz; and (xxv) >10.0MHz.

Singly charged ions having a mass to charge ratio in the range of 1-100,100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900,900-1000 or >1000 preferably have a drift or transit time through thefirst ion guide in the range: (i) 0-10 μs; (ii) 10-20 μs; (iii) 20-30μs; (iv) 30-40 μs; (v) 40-50 μs; (vi) 50-60 μs; (vii) 60-70 μs; (viii)70-80 μs; (ix) 80-90 μs; (x) 90-100 μs; (xi) 100-110 μs; (xii) 110-120μs; (xiii) 120-130 μs; (xiv) 130-140 μs; (xv) 140-150 μs; (xvi) 150-160μs; (xvii) 160-170 μs; (xviii) 170-180 μs; (xix) 180-190 μs; (xx)190-200 μs; (xxi) 200-210 μs; (xxii) 210-220 μs; (xxiii) 220-230 μs;(xxiv) 230-240 μs; (xxv) 240-250 μs; (xxvi) 250-260 μs; (xxvii) 260-270μs; (xxviii) 270-280 μs; (xxix) 280-290 μs; (xxx) 290-300 μs; and(xxxi) >300 μs.

The apparatus preferably further comprises a device arranged and adaptedto maintain at least a portion of the first ion guide at a pressureselected from the group consisting of: (i) ≦0.1 mbar; (ii) ≧0.1 mbar;(iii) ≧0.2 mbar; (iv) ≧0.3 mbar; (v) ≧0.4 mbar; (vi) ≧0.5 mbar; (vii)≧0.6 mbar; (viii) ≧0.7 mbar; (ix) ≧0.8 mbar; (x) ≧0.9 mbar; (xi) ≧1.0mbar; (xii) ≧1.1 mbar; (xiii) ≧1.2 mbar; (xiv) ≧1.3 mbar; (xv) ≧1.4mbar; (xvi) ≧1.5 mbar; (xvii) ≧1.6 mbar; (xviii) ≧1.7 mbar; (xix) ≧1.8mbar; (xx) ≧1.9 mbar; (xxi) ≧2.0 mbar; (xxii) ≧3.0 mbar; (xxiii) ≧4.0mbar; (xxiv) ≧5.0 mbar; (xxv) ≧6.0 mbar; (xxvi) ≧7.0 mbar; (xxvii) ≧8.0mbar; (xxviii) ≧9.0 mbar; and (xxix) ≧10.0 mbar.

The apparatus preferably further comprises a device arranged and adaptedto maintain at least a portion of the first ion guide at a pressureselected from the group consisting of: (i) 0.1-0.5 mbar; (ii) 0.5-1.0mbar; (iii) 1.0-1.5 mbar; (iv) 1.5-2.0 mbar; (v) 2.0-2.5 mbar; (vi)2.5-3.0 mbar; (vii) 3.0-3.5 mbar; (viii) 3.5-4.0 mbar; (ix) 4.0-4.5mbar; (x) 4.5-5.0 mbar; (xi) 5.0-5.5 mbar; (xii) 5.5-6.0 mbar; (xiii)6.0-6.5 mbar; (xiv) 6.5-7.0 mbar; (xv) 7.0-7.5 mbar; (xvi) 7.5-8.0 mbar;(xvii) 8.0-8.5 mbar; (xviii) 8.5-9.0 mbar; (xix) 9.0-9.5 mbar; and (xx)9.5-10.0 mbar.

The first ion guide is preferably arranged and adapted to receive a beamof ions and to convert or partition the beam of ions such that at least1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20separate groups or packets of ions are confined and/or isolated in thefirst ion guide at any particular time, and wherein each group or packetof ions is preferably separately confined and/or isolated in a separateaxial potential well formed in the first ion guide.

A first voltage means is preferably arranged and adapted to create atleast 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19or 20 separate axial potential wells which are substantiallysimultaneously translated along at least 5%, 10%, 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100%of the length of the first ion guide.

The first ion guide is preferably arranged and adapted to retain and/orconfine and/or partition ions which are received by the first ion guideand to translate ions in one or more groups or packets of ions along atleast 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% of the axial length of the firstion guide whilst either: (i) substantially maintaining the order and/orfidelity in which ions are received by the first ion guide; and/or (ii)substantially maintaining the composition of ions as one or more groupsor packets of ions are translated along the first ion guide.

The first ion guide is preferably arranged and adapted to collisionallycool, substantially thermalise or substantially reduce the kineticenergy of ions within the first ion guide.

The second chamber preferably comprises a housing having a second gasoutlet and an ion exit aperture.

The second gas or mixture of gases preferably comprises one or moregases selected from the group consisting of: (i) helium; (ii) hydrogen;(iii) neon; (iv) methane; (v) ammonia; (vi) nitrogen; (vii) argon;(viii) xenon; (ix) air; and (x) SF6 or sulphur hexafluoride.

According to an embodiment the second gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% helium.

According to an embodiment the second gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% hydrogen.

According to an embodiment the second gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% neon.

According to an embodiment the second gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% methane.

According to an embodiment the second gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% ammonia.

According to an embodiment the second gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% nitrogen.

According to an embodiment the second gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% argon.

According to an embodiment the second gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% xenon.

According to an embodiment the second gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% air.

According to an embodiment the second gas or mixture of gases comprisesat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% SF6 or sulphur hexafluoride.

The second gas or mixture of gases is preferably provided at a pressureselected from the group consisting of: (i) <0.1 mbar; (ii) ≧0.1 mbar;(iii) ≧0.2 mbar; (iv) ≧0.3 mbar; (v) ≧0.4 mbar; (vi) ≧0.5 mbar; (vii)≧0.6 mbar; (viii) ≧0.7 mbar; (ix) ≧0.8 mbar; (x) ≧0.9 mbar; (xi) ≧1.0mbar; (xii) ≧1.1 mbar; (xiii) ≧1.2 mbar; (xiv) ≧1.3 mbar; (xv) ≧1.4mbar; (xvi) ≧1.5 mbar; (xvii) ≧1.6 mbar; (xviii) ≧1.7 mbar; (xix) ≧1.8mbar; (xx) ≧1.9 mbar; (xxi) ≧2.0 mbar; (xxii) ≧3.0 mbar; (xxiii) ≧4.0mbar; (xxiv) ≧5.0 mbar; (xxv) ≧6.0 mbar; (xxvi) ≧7.0 mbar; (xxvii) ≧8.0mbar; (xxviii) ≧9.0 mbar; and (xxix) ≧10.0 mbar.

The second gas or mixture of gases is preferably provided at a pressureselected from the group consisting of: (i) 0.1-0.5 mbar; (ii) 0.5-1.0mbar; (iii) 1.0-1.5 mbar; (iv) 1.5-2.0 mbar; (v) 2.0-2.5 mbar; (vi)2.5-3.0 mbar; (vii) 3.0-3.5 mbar; (viii) 3.5-4.0 mbar; (ix) 4.0-4.5mbar; (x) 4.5-5.0 mbar; (xi) 5.0-5.5 mbar; (xii) 5.5-6.0 mbar; (xiii)6.0-6.5 mbar; (xiv) 6.5-7.0 mbar; (xv) 7.0-7.5 mbar; (xvi) 7.5-8.0 mbar;(xvii) 8.0-8.5 mbar; (xviii) 8.5-9.0 mbar; (xix) 9.0-9.5 mbar; and (xx)9.5-10.0 mbar.

The second chamber preferably has a length selected from the groupconsisting of: (i) <20 mm; (ii) 20-40 mm; (iii) 40-60 mm; (iv) 60-80 mm;(v) 80-100 mm; (vi) 100-120 mm; (vii) 120-140 mm; (viii) 140-160 mm;(ix) 160-180 mm; (x) 180-200 mm; (xi) 200-220 mm; (xii) 220-240 mm;(xiii) 240-260 mm; (xiv) 260-280 mm; (xv) 280-300 mm; and (xvi) >300 mm.

The ion mobility spectrometer or separator preferably comprises a gasphase electrophoresis device.

The ion mobility spectrometer or separator preferably comprises:

(i) a drift tube;

(ii) a multipole rod set or a segmented multipole rod set;

(iii) an ion tunnel or ion funnel; or

(iv) a stack or array of planar, plate or mesh electrodes.

The drift tube preferably comprises one or more electrodes and means formaintaining an axial DC voltage gradient or a substantially constant orlinear axial DC voltage gradient along at least 5%, 10%, 15%, 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or100% of the axial length of the drift tube.

The multipole rod set preferably comprises a. quadrupole rod set, ahexapole rod set, an octapole rod set or a rod set comprising more thaneight rods.

The ion tunnel or ion funnel preferably comprises a plurality ofelectrodes or at least 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100electrodes having apertures through which ions are transmitted in use,wherein at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the electrodes haveapertures which are of substantially the same size or area or which haveapertures which become progressively larger and/or smaller in size or inarea. According to an embodiment at least 5%, 10%, 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100%of the electrodes have internal diameters or dimensions selected fromthe group consisting of: (i) ≦1.0 mm; (ii) ≦2.0 mm; (iii) ≦3.0 mm; (iv)≦4.0 mm; (v) ≦5.0 mm; (vi) ≦6.0 mm; (vii) ≦7.0 mm; (viii) ≦8.0 mm; (ix)≦9.0 mm; (x) ≦10.0 mm; and (xi) ≧10.0 mm.

The stack or array of planar, plate or mesh electrodes preferablycomprises a plurality or at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19 or 20 planar, plate or mesh electrodeswherein at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the planar, plate ormesh electrodes are arranged generally in the plane in which ions travelin use. At least some or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%,45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of theplanar plate or mesh electrodes are preferably supplied with an AC or RFvoltage and wherein adjacent planar, plate or mesh electrodes aresupplied with opposite phases of the AC or RF voltage.

The ion mobility spectrometer or separator preferably comprises aplurality of axial segments or at least 5, 10, 15, 20, 25, 30, 35, 40,45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 axial segments.

The apparatus may further comprise DC voltage means for maintaining asubstantially constant DC voltage gradient along at least a portion orat least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% of the axial length of the ionmobility spectrometer or separator in order to urge at least some ionsalong at least a portion or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%,40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% ofthe axial length of the ion mobility spectrometer or separator.

The apparatus may further comprise transient DC voltage means arrangedand adapted to apply one or more transient DC voltages or potentials orone or more transient DC voltage or potential waveforms to electrodesforming the ion mobility spectrometer or separator in order to urge atleast some ions along at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%,45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of theaxial length of the ion mobility spectrometer or separator.

The apparatus may further comprise AC or RF voltage means arranged andadapted to apply two or more phase-shifted AC or RF voltages toelectrodes forming the ion mobility spectrometer or separator in orderto urge at least some ions along at least 5%, 10%, 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100%of the axial length of the ion mobility spectrometer or separator.

The ion mobility spectrometer or separator preferably has an axiallength selected from the group consisting of: (i) <20 mm; (ii) 20-40 mm;(iii) 40-60 mm; (iv) 60-80 mm; (v) 80-100 mm; (vi) 100-120 mm; (vii)120-140 mm; (viii) 140-160 mm; (ix) 160-180 mm; (x) 180-200 mm; (xi)200-220 mm; (xii) 220-240 mm; (xiii) 240-260 mm; (xiv) 260-280 mm; (xv)280-300 mm; and (xvi) >300 mm.

The ion mobility spectrometer or separator preferably further comprisesAC or RF voltage means arranged and adapted to apply an AC or RF voltageto at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%,65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the electrodes forming theion mobility spectrometer or separator in order to confine ions radiallywithin the ion mobility spectrometer or separator.

The AC or RF voltage means is preferably arranged and adapted to supplyan AC or RF voltage to the electrodes of the ion mobility spectrometeror separator having an amplitude selected from the group consisting of:(i) <50 V peak to peak; (ii) 50-100 V peak to peak; (iii) 100-150 V peakto peak; (iv) 150-200 V peak to peak; (v) 200-250 V peak to peak; (vi)250-300 V peak to peak; (vii) 300-350 V peak to peak; (viii) 350-400 Vpeak to peak; (ix) 400-450 V peak to peak; (x) 450-500 V peak to peak;and (xi) ≧500 V peak to peak. The AC or RF voltage means is preferablyarranged and adapted to supply an AC or RF voltage to the electrodes ofthe ion mobility spectrometer or separator having a frequency selectedfrom the group consisting of: (i) ≦100 kHz; (ii) 100-200 kHz; (iii)200-300 kHz; (iv) 300-400 kHz; (v) 400-500 kHz; (vi) 0.5-1.0 MHz; (vii)1.0-1.5 MHz; (viii) 1.5-2.0 MHz; (ix) 2.0-2.5 MHz; (x) 2.5-3.0 MHz; (xi)3.0-3.5 MHz; (xii) 3.5-4.0 MHz; (xiii) 4.0-4.5 MHz; (xiv) 4.5-5.0 MHz;(xv) 5.0-5.5 MHz; (xvi) 5.5-6.0 MHz; (xvii) 6.0-6.5 MHz; (xviii) 6.5-7.0MHz; (xix) 7.0-7.5 MHz; (xx) 7.5-8.0 MHz; (xxi) 8.0-8.5 MHz; (xxii)8.5-9.0 MHz; (xxiii) 9.0-9.5 MHz; (xxiv) 9.5-10.0 MHz; and (xxv) >10.0MHz.

According to an embodiment singly charged ions having a mass to chargeratio in the range of 1-100, 100-200, 200-300, 300-400, 400-500,500-600, 600-700, 700-800, 800-900, 900-1000 or >1000 preferably have adrift or transit time through the ion mobility spectrometer or separatorin the range: (i) 0-1 ms; (ii) 1-2 ms; (iii) 2-3 ms; (iv) 3-4 ms; (v)4-5 ms; (vi) 5-6 ms; (vii) 6-7 ms; (viii) 7-8 ms; (ix) 8-9 ms; (x) 9-10ms; (xi) 10-11 ms; (xii) 11-12 ms; (xiii) 12-13 ms; (xiv) 13-14 ms; (xv)14-15 ms; (xvi) 15-16 ms; (xvii) 16-17 ms; (xviii) 17-18 ms; (xix) 18-19ms; (xx) 19-20 ms; (xxi) 20-21 ms; (xxii) 21-22 ms; (xxiii) 22-23 ms;(xxiv) 23-24 ms; (xxv) 24-25 ms; (xxvi) 25-26 ms; (xxvii) 26-27 ms;(xxviii) 27-28 ms; (xxix) 28-29 ms; (xxx) 29-30 ms; (xxxi) 30-35 ms;(xxxii) 35-40 ms; (xxxiii) 40-45 ms; (xxxiv) 45-50 ms; (xxxv) 50-55 ms;(xxxvi) 55-60 ms; (xxxvii) 60-65 ms; (xxxviii) 65-70 ms; (xxxix) 70-75ms; (xl) 75-80 ms; (xli) 80-85 ms; (xlii) 85-90 ms; (xliii) 90-95 ms;(xliv) 95-100 ms; and (xlv) >100 ms.

According to an embodiment the apparatus further comprises a devicearranged and adapted to maintain at least a portion of the ion mobilityspectrometer or separator at a pressure selected from the groupconsisting of: (i) >0.001 mbar; (ii) ≧0.01 mbar; (iii) ≧0.1 mbar; (iv)≧1 mbar; (v) ≧10 mbar; (vi) ≧100 mbar; (vii) 0.001-100 mbar; (viii)0.01-10 mbar; and (ix) 0.1-1 mbar.

According to an embodiment the apparatus further comprises a devicearranged and adapted to maintain at least a portion of the ion mobilityspectrometer or separator at a pressure selected from the groupconsisting of: (i) ≦0.1 mbar; (ii) ≧0.1 mbar; (iii) ≧0.2 mbar; (iv) ≧0.3mbar; (v) ≧0.4 mbar; (vi) ≧0.5 mbar; (vii) ≧0.6 mbar; (viii) ≧0.7 mbar;(ix) ≧0.8 mbar; (x) ≧0.9 mbar; (xi) ≧1.0 mbar; (xii) ≧1.1 mbar; (xiii)≧1.2 mbar; (xiv) ≧1.3 mbar; (xv) ≧1.4 mbar; (xvi) ≧1.5 mbar; (xvii) ≧1.6mbar; (xviii) ≧1.7 mbar; (xix) ≧1.8 mbar; (xx) ≧1.9 mbar; (xxi) ≧2.0mbar; (xxii) ≧3.0 mbar; (xxiii) ≧4.0 mbar; (xxiv) ≧5.0 mbar; (xxv) ≧6.0mbar; (xxvi) ≧7.0 mbar; (xxvii) ≧8.0 mbar; (xxviii) ≧9.0 mbar; and(xxix) ≧10.0 mbar.

According to an embodiment the apparatus further comprises a devicearranged and adapted to maintain at least a portion of the ion mobilityspectrometer or separator at a pressure selected from the groupconsisting of: (i) 0.1-0.5 mbar; (ii) 0.5-1.0 mbar; (iii) 1.0-1.5 mbar;(iv) 1.5-2.0 mbar; (v) 2.0-2.5 mbar; (vi) 2.5-3.0 mbar; (vii) 3.0-3.5mbar; (viii) 3.5-4.0 mbar; (ix) 4.0-4.5 mbar; (x) 4.5-5.0 mbar; (xi)5.0-5.5 mbar; (xii) 5.5-6.0 mbar; (xiii) 6.0-6.5 mbar; (xiv) 6.5-7.0mbar; (xv) 7.0-7.5 mbar; (xvi) 7.5-8.0 mbar; (xvii) 8.0-8.5 mbar;(xviii) 8.5-9.0 mbar; (xix) 9.0-9.5 mbar; and (xx) 9.5-10.0 mbar.

The apparatus preferably further comprises a vacuum chamber which housesthe first chamber and the second chamber. The vacuum chamber preferablycomprises an entrance differential pumping aperture, an exitdifferential pumping aperture and a port connected to a vacuum pump.

The apparatus preferably further comprises one or more further ionguides arranged between the entrance differential pumping aperture andthe first chamber and/or between the second chamber and the exitdifferential pumping aperture. The one or more further ion guidespreferably have a length selected from the group consisting of: (i) <20mm; (ii) 20-40 mm; (iii) 40-60 mm; (iv) 60-80 mm; (v) 80-100 mm; (vi)100-120 mm; (vii) 120-140 mm; (viii) 140-160 mm; (ix) 160-180 mm; (x)180-200 mm; (xi) 200-220 mm; (xii) 220-240 mm; (xiii) 240-260 mm; (xiv)260-280 mm; (xv) 280-300 mm; and (xvi) >300 mm.

According to an embodiment the one or more further ion guides maycomprise:

(i) one or more multipole rod set or a segmented multipole rod sets;

(ii) one or more ion tunnels or ion funnels; or

(iii) one or more stacks or arrays of planar, plate or mesh electrodes.

According to an embodiment the apparatus further comprises means forpulsing ions into the ion mobility spectrometer or separator once every0-5 ms, 5-10 ms, 10-15 ms, 15-20 ms, 20-25 ms, 25-30 ms, 30-35 ms, 35-40ms, 40-45 ms, 45-50 ms, 50-55 ms, 55-60 ms, 60-65 ms, 65-70 ms, 70-75ms, 75-80 ms, 80-85 ms, 85-90 ms, 90-95 ms, 95-100 ms or >100 ms.

According to another aspect of the present invention there is provided amass spectrometer comprising apparatus as described above.

The mass spectrometer preferably further comprises an ion source. Theion source is preferably selected from the group consisting of: (i) anElectrospray ionisation (“ESI”) ion source; (ii) an Atmospheric PressurePhoto Ionisation (“APPI”) ion source; (iii) an Atmospheric PressureChemical Ionisation (“APCI”) ion source; (iv) a Matrix Assisted LaserDesorption Ionisation (“MALDI”) ion source; (v) a Laser DesorptionIonisation (“LDI”) ion source; (vi) an Atmospheric Pressure Ionisation(“API”) ion source; (vii) a Desorption Ionisation On Silicon (“DIOS”)ion source; (viii) an Electron Impact (“EI”) ion source; (ix) a ChemicalIonisation (“CI”) ion source; (x) a Field Ionisation (“FI”) ion source;(xi) a Field Desorption (“FD”) ion source; (xii) an Inductively CoupledPlasma (“ICP”) ion source; (xiii) a Fast Atom Bombardment (“FAB”) ionsource; (xiv) a Liquid Secondary Ion Mass Spectrometry (“LSIMS”) ionsource; (xv) a Desorption Electrospray Ionisation (“DESI”) ion source;(xvi) a Nickel-63 radioactive ion source; (xvii) an Atmospheric PressureMatrix Assisted Laser Desorption Ionisation ion source; and (xviii) aThermospray ion source.

The ion source preferably comprises a pulsed or continuous ion source.

The mass spectrometer preferably further comprises a mass analyser. Themass analyser is preferably selected from the group consisting of: (i) aquadrupole mass analyser; (ii) a 2D or linear quadrupole mass analyser;(iii) a Paul or 3D quadrupole mass analyser; (iv) a Penning trap massanalyser; (vY an ion trap mass analyser; (vi) a magnetic sector massanalyser; (vii) Ion Cyclotron Resonance (“ICR”) mass analyser; (viii) aFourier Transform Ion Cyclotron Resonance (“FTICR”) mass analyser; (ix)an electrostatic or orbitrap mass analyser; (x) a Fourier Transformelectrostatic or orbitrap mass analyser; (xi) a Fourier Transform massanalyser; (xii) a Time of Flight mass analyser; (xiii) an orthogonalacceleration Time of Flight mass analyser; and (xiv) an axialacceleration Time of Flight mass analyser.

The mass spectrometer preferably further comprises an ion detector.

According to another aspect of the present invention there is provided amethod comprising:

providing a first chamber;

providing a second chamber located downstream of the first chamber;

providing an ion mobility spectrometer or separator located in thesecond chamber;

providing a first gas or mixture of gases to the first chamber, thefirst gas or mixture of gases having a first average density ormolecular weight M₁; and

providing a second gas or mixture of gases to the second chamber, thesecond gas or mixture of gases having a second average density ormolecular weight M₂, wherein M₁<M₂.

According to another aspect of the present invention there is provided amethod of mass spectrometry comprising a method as disclosed above.

According to another aspect of the present invention there is providedapparatus comprising:

a first chamber comprising an ion inlet aperture and a first gas outlet;

a second chamber located downstream of the first chamber, the secondchamber comprising a second gas outlet and an ion outlet aperture;

an inter-chamber aperture between the first chamber and the secondchamber;

an ion guide locatediin the first chamber;

an ion mobility spectrometer or separator located in the second chamber;

a device for providing a first gas or mixture of gases to the firstchamber, the first gas or mixture of gases having a first averagedensity or molecular weight M₁; and

a device for providing a second gas or mixture of gases to the secondchamber, the second gas or mixture of gases having a second averagedensity or molecular weight M₂, wherein M₂/M₁≧4.

The first chamber and the second chamber are preferably located withinthe same vacuum chamber. The vacuum chamber preferably comprises anentrance differential pumping aperture, an exit differential pumpingaperture and a port connected to a vacuum pump.

According to another aspect of the present invention there is provided amethod comprising:

providing a first chamber comprising an ion inlet aperture and a firstgas outlet;

providing a second chamber located downstream of the first chamber, thesecond chamber comprising a second gas outlet and an ion outletaperture;

providing an inter-chamber aperture between the first chamber and thesecond chamber;

providing an ion guide located in the first chamber;

providing an ion mobility spectrometer or separator located in thesecond chamber;

providing a first gas or mixture of gases to the first chamber, thefirst gas or mixture of gases having a first average density ormolecular weight M₁; and

providing a second gas or mixture of gases to the second chamber, thesecond gas or mixture of gases having a second average density ormolecular weight M₂, wherein M₂/M₁≧4.

The method preferably further comprises locating the first chamber andthe second chamber within the same vacuum chamber. The vacuum chamberpreferably comprises an entrance differential pumping aperture, an exitdifferential pumping aperture and a port connected to a vacuum pump.

According to the preferred embodiment helium gas is preferably providedin or to. the first chamber. Helium gas is particularly advantageoussince it results in low centre-of-mass collision energies with ions andhence ions entering the first chamber will preferably not besubstantially fragmented. Furthermore, ions possess a relatively highionic mobility as they pass through helium gas and hence ions willpreferably not suffer from ion mobility discrimination effects.Therefore, according to an embodiment a relatively low strength electricfield may be used to drive or inject ions into the chamber housing theion mobility spectrometer and the possibility of undesired ionfragmentation and undesired ion mobility discrimination effects prior toions entering the chamber housing the ion mobility spectrometer can beconsiderably reduced.

According to the preferred embodiment the ion mobility spectrometer orseparator is preferably provided at sub-atmospheric pressure. The ionmobility spectrometer or separator preferably exhibits good separationcharacteristics without use of excessively high gas pressures. The ionmobility spectrometer or separator preferably comprises a chamber whichis divided into two sub-chambers which are preferably maintained atsubstantially the same pressure and which are preferably separated by anaperture. The first sub-chamber preferably predominantly contains arelatively light gas, such as helium, and preferably minimises ionfragmentation and/or discrimination effects as ions enter the firstsub-chamber from a relatively low pressure chamber or region. The secondsub-chamber preferably predominantly contains a relatively heavy gas,such as argon or nitrogen, and preferably provides good ion mobilityseparation characteristics for the ions.

Various embodiments of the present invention together with anarrangement which is presented for illustration purposes will now bedescribed, by way of example only, and with reference to theaccompanying drawings in which:

FIG. 1 shows a conventional ion mobility separator or spectrometerlocated in an IMS chamber which is maintained at sub-atmosphericpressure and wherein the IMS chamber is located within a differentialvacuum chamber; and

FIG. 2 shows an embodiment of the present invention wherein an ionmobility spectrometer or separator is arranged in a second chamber whichis supplied with a relatively heavy gas such as argon or nitrogen andwherein a first chamber is arranged upstream which is supplied with arelatively light gas such as helium and wherein both the first andsecond chambers are located within a differential vacuum chamber.

A section or portion of a conventional ion mobility spectrometer isshown in FIG. 1. A differential pumping chamber 1 is shown having anentrance differential pumping aperture 2 and an exit differentialpumping aperture 3. An ion mobility spectrometer or separator 6 isprovided within an IMS chamber 5. The IMS chamber 5 has an entrance 7and an exit 8 and is located within the differential pumping chamber 1.Additional vacuum chambers (not shown) are located upstream anddownstream of the differential pumping chamber 1 shown in FIG. 1.

The ion mobility spectrometer 6 is filled or supplied with gas via a gasoutlet 9. The gas exits the IMS chamber 5 via both the entrance aperture7 and the exit aperture 8 into the differential vacuum chamber 1 whichsurrounds the IMS chamber 5. The differential vacuum chamber 1 is pumpedby a vacuum pump (not shown) which is connected to the differentialvacuum chamber 1 via a port 4 in order to maintain the differentialvacuum chamber 1 at a lower pressure than the pressure within the IMSchamber 5. Gas egress from the differential vacuum chamber 1 intoadjoining vacuum chambers (not shown) is minimised through use ofconductance limiting differential apertures 2,3.

According to a known arrangement, ions pass from a relatively lowpressure region upstream of the differential vacuum chamber 1 throughthe entrance differential pumping aperture 2 and into the differentialvacuum chamber 1. The neutral gas in which ion mobility separation takesplace is supplied to the IMS chamber 5 via the gas outlet 9. The gaswhich is supplied to the IMS chamber 5 exits through the entranceaperture 7 and the exit aperture 8 into the surrounding differentialchamber 1. Ions entering the differential vacuum chamber 1 through theentrance differential aperture 2 therefore need to be driven into theIMS chamber 5 through the entrance aperture 7 against a significantoutflow of relatively heavy gas which escapes from the IMS chamber 5 andwhich opposes the onward transmission of ions into the IMS chamber 5.Ions are driven into the IMS chamber 5 by arranging for the ions to haverelatively high initial ion energies and by maintaining a relativelystrong electric field between the entrance differential pumping aperture2 and the ion mobility spectrometer 6 in order to urge ions into the IMSchamber 5.

Once ions have been urged into the IMS chamber 5 the ions then undergoion mobility separation in the ion mobility spectrometer 6 which islocated in the IMS chamber 5. Ions which have been separated accordingto their ion mobility emerge from the exit of the ion mobilityspectrometer 6 and exit the IMS chamber 5 along with gas from the IMSchamber 5 via the exit aperture 8 into the differential vacuum chamber1. The ions then exit the differential chamber 1 via the exitdifferential aperture 3. The ions are then onwardly transmitted tofurther sections of the mass spectrometer which are arranged downstreamof the differential vacuum chamber 1 for further analysis and/ordetection.

According to the known arrangement, ions are driven into the IMS chamber5 against a backflow or outflow of the gas which is used or provided forion mobility separation and may have a relatively high molecular weight.Ions may disadvantageously be caused to fragment as they are driven intothe IMS chamber 5. Ions may also disadvantageously suffer from undesiredion mobility effects as the ions enter the IMS chamber 5. The ionmobility spectrometer 6 is operated or maintained at a relatively highpressure but this can put a relatively high demand on the vacuum pumprequirement. Furthermore, relatively small entrance and exit aperturesmust be used and this can reduce ion transmission through the system.

FIG. 2 shows a section or portion of an ion mobility spectrometeraccording to a preferred embodiment of the present invention. An ionmobility spectrometer or separator 6 is provided within an IMS chamber5. An injection chamber 10 having an entrance aperture 11 is preferablyprovided upstream of the IMS chamber 5. The injection chamber 10 ispreferably connected to the IMS chamber 5 (or communicates with the IMSchamber 5) via an inter-chamber aperture 12. An ion guide 13 ispreferably located or provided in the injection chamber 10. The ionguide 13 is preferably arranged to transport ions efficiently from theinlet aperture 11 of the injection chamber 10 to the inter-chamberaperture 12 which is arranged between the injection chamber 10 and theIMS chamber 5. The ion guide 13 is therefore preferably arranged totransmit ions onwardly to the ion mobility spectrometer or separator 6.

The injection chamber 10 is preferably maintained at a given pressureand is supplied with a first gas or mixture of gases which is preferablyemitted via or from a first gas outlet 14. The first gas or mixture ofgases preferably exits the injection chamber 10 substantially throughthe entrance aperture 11 of the injection chamber 10.

The IMS chamber 5 is preferably maintained at a given pressure and issupplied with a second gas or mixture of gases which is preferablyemitted via or from a second gas outlet 9. The second gas or mixture ofgases preferably exits the IMS chamber 5 substantially through the exitaperture 8 of the IMS chamber 5.

The injection chamber 10 and the IMS chamber 5 are preferably housed orprovided within the same differential vacuum chamber 1. The differentialvacuum chamber 1 is preferably maintained at a pressure below that ofthe injection chamber 10 and that of the IMS chamber 5 by direct pumpingby a vacuum pump (not shown) which is connected to the differentialvacuum chamber 1 via port 4. Vacuum chambers (not shown) locatedupstream and downstream of the differential vacuum chamber 1 preferablyhave minimal gas loading from the differential vacuum chamber 1 due toconductance limiting entrance differential aperture 1 and conductancelimiting exit differential aperture 3.

Ions preferably enter the differential vacuum chamber 1 via an entrancedifferential aperture 2. The ions are then preferably driven or urgedinto the injection chamber 10 via the entrance aperture 11. Ions arethen preferably transmitted along and through the injection chamber 10by being transmitted along an ion guide 13 arranged in the injectionchamber 10. The ions then preferably pass from the injection chamber 10to the IMS chamber 5 via the inter-chamber aperture 12. The ions arethen preferably caused to pass along and through the ion mobilityspectrometer or separator 6 which is arranged in the IMS chamber 5. Theions are preferably separated temporally as they pass along and throughthe ion mobility spectrometer or separator 6. The ions then preferablyexit the ion mobility spectrometer or separator 6 and the IMS chamber 5via the exit aperture 8. The ions are then preferably transmittedthrough the differential vacuum chamber 1 and preferably exit thedifferential vacuum chamber 1 via the exit differential aperture 3.

According to the preferred embodiment the first gas or mixture of gaseswhich preferably fills or which is supplied to the injection chamber 10is preferably chosen such that minimal ion fragmentation and/ordiscrimination effects occur as ions are transmitted or injected intothe injection chamber 10 and as the ions transit through the injectionchamber 10. The first gas or mixture of gases preferably compriseshelium gas although other gases may be used according to other lesspreferred embodiments.

The second gas or mixture of gases which preferably fills or which issupplied to the IMS chamber 5 is preferably chosen such that efficiention mobility separation is preferably achieved within the ion mobilityspectrometer or separator 6. The second gas or mixture of gasespreferably comprises argon or nitrogen gas although other gases may beused according to other less preferred embodiments.

The flow rates of the first gas or mixture of gases and the second gasor mixture of gases into their respective chambers 10,5 may be arrangedsuch that the chamber pressures are substantially the same. Therefore,according to the preferred embodiment there may be essentially no netflow of gas through the inter-chamber aperture 12. To a firstapproximation at least, substantially all of the first gas or mixture ofgases which is provided or supplied to the injection chamber 10 via thefirst gas outlet 14 may be considered as exiting the injection chamber10 via the entrance aperture 11. Similarly, substantially all of thesecond gas or mixture of gases which is provided or supplied to the IMSchamber 5 via the second gas outlet 9 may be considered as exiting theIMS chamber 5 via the exit aperture 8.

In practice, there may be a small amount of diffusional mixing of gasesat the inter-chamber aperture 5 or the boundary between the injectionchamber 10 and the IMS chamber 5. Furthermore, slight imbalances inpressure between the two chambers 10,5 may result in a small net gasflow from one chamber to the other. However, according to the preferredembodiment the degree of mixing of the first gas or mixture of gases andthe second gas or mixture of gases is preferably minimal.

According to the preferred embodiment one or more packets of ions whichare desired to be separated according to their ion mobility preferablyenter the differential vacuum chamber 1 from a relatively low pressureregion via the conductance limiting entrance differential aperture 2.Ions are then preferably driven into the injection chamber 10 via theentrance aperture 11 against the outflow of the first gas or mixture ofgases from the injection chamber 10. The ions may be driven into theinjection chamber 10 by ensuring that the ions have a relatively highinitial ion energy and/or by maintaining an appropriate electric fieldbetween the entrance differential aperture 2 and the injection chamber10 which urges ions into the injection chamber 10. Ions in the injectionchamber 10 are preferably confined and onwardly transmitted by the ionguide 13. The ions then preferably exit the ion guide 13 and preferablymigrate or are otherwise transmitted through the first gas or mixture ofgases and pass through the inter-chamber aperture 12. The ionspreferably pass through the inter-chamber aperture 12 into the IMSchamber 5 which is preferably filled with the second gas or mixture ofgases. The ions then preferably undergo ion mobility-based separation inthe ion mobility spectrometer or separator 6 located within the IMSchamber 5. The mobility separated ions then preferably exit the ionmobility spectrometer or separator 6 and the IMS chamber 5 andpreferably pass via the exit aperture 8 into the differential vacuumchamber 1. The ions are then preferably transmitted to the exitdifferential aperture 3 and the ions then preferably exit thedifferential vacuum chamber 1 to a lower pressure region via theconductance limiting exit differential aperture 3. The ions are thenpreferably onwardly transmitted for further analysis and/or detection. Amass analyser and ion detector is preferably located in a vacuum chamber(not shown) which is preferably arranged downstream of the differentialvacuum chamber 1.

According to an embodiment ions initially entering the differentialvacuum chamber 1 may pass through a mass filtering device such as aquadrupole rod set operated as a band-pass device in an RF-only mode ofoperation or as a mass to charge ratio selective filter in an RF/DC modeof operation.

The ion guide 13 arranged in the injection chamber 10 preferablycomprises a plurality of electrodes having apertures through which ionsare transmitted in use. One or more transient DC voltages or potentialsor one or more transient DC voltage or potential waveforms arepreferably applied to the electrodes of the ion guide 13 in order tourge or propel ions along the length of the ion guide 13 by creating aplurality of real axial potential wells which are translated along theion guide 13. Ions are preferably propelled through the inter-chamberaperture 12 by the application of the one or more transient DC voltagesor potentials or the one or more transient DC voltage or potentialwaveforms to the electrodes forming the ion guide 13.

The ion mobility spectrometer or separator 6 preferably comprises aplurality of electrodes having apertures through which ions aretransmitted in use. One or more transient DC voltages or potentials orone or more DC voltage or potential waveforms are preferably applied tothe electrodes of the ion mobility spectrometer or separator 6 in orderto urge ions along the length of the ion mobility spectrometer orseparator 6. The gas pressure in the injection chamber 10 and/or in theIMS chamber 5 is preferably maintained in the range of 0.2 mbar to 2mbar.

According to an embodiment ions exiting the differential vacuum chamber1 are preferably transmitted to a mass spectrometer such as a quadrupolemass filter, a linear or two dimensional quadrupole ion trap, a Paul orthree dimensional quadrupole ion trap, a Time of Flight massspectrometer, an orthogonal acceleration Time of Flight massspectrometer, a Fourier Transform ICR mass spectrometer, a FourierTransform Orbitrap mass spectrometer or a magnetic sector massspectrometer.

Further embodiments are contemplated wherein other types of ionfiltering/analysis may be employed prior to ions entering into thedifferential vacuum chamber 1.

The ion guide 13 in the injection chamber 10 may according to anotherembodiment comprise a multipole rod set ion guide or a DC-only ringstack ion guide. Axial DC electric fields may or may not be used todrive or urge ions along and through the first gas or mixture of gasespresent in the injection chamber 10.

The ion mobility spectrometer or separator 6 located in the IMS chamber5 may according to one embodiment comprise a multipole rod set device ora DC-only stacked ring device. Axial DC voltage gradients may be used toeffect ion mobility separation in the presence of the second gas ormixture of gases.

According to an embodiment ions may enter the differential vacuumchamber 1 in a continuous stream or in a pulsed manner.

According to an embodiment ions may be stored for a given time period inthe ion guide 13 prior to being released in a gated manner into the IMSchamber 5.

According to an embodiment one or more additional ion guides (not shown)may be arranged in the differential vacuum chamber 1 between theentrance differential aperture 2 and the entrance aperture 11 to theinjection chamber 10.

According to an embodiment one or more additional ion guides (not shown)may be arranged in the differential chamber 1 between the exit aperture8 of the IMS chamber 5 and the exit differential aperture 3.

The one or more additional ion guides may be arranged to store and/ortransport and/or manipulate ions.

Although the present invention has been described with reference topreferred embodiments, it will be apparent to those skilled in the artthat various modifications in form and detail may be made withoutdeparting from the scope of the present invention as set forth in theaccompanying claims.

1. Apparatus comprising: a first chamber; a second chamber locateddownstream of said first chamber; an ion guide comprising a plurality ofelectrodes located in said first chamber; an ion mobility spectrometeror separator located in said second chamber; a device for providing afirst gas or mixture of gases to said first chamber, said first gas ormixture of gases having a first average density or molecular weight M₁;and a device for providing a second gas or mixture of gases to saidsecond chamber, said second gas or mixture of gases having a secondaverage density or molecular weight M₂, wherein M₁<M₂.
 2. Apparatus asclaimed in claim 1, wherein the ratio M₂/M₁ is selected from the groupconsisting of: (i) ≧1.1; (ii) ≧1.5; (iii) ≧2.0; (iv) ≧3.0; (v) ≧4.0;(vi) ≧5.0; (vii) ≧6.0; (viii) ≧7.0; (ix) ≧8.0; (x) ≧9.0; (xi) ≧10.0;(xii) ≧11.0; (xiii) ≧12.0; (xiv) ≧13.0; (xv) ≧14.0; (xvi) ≧15.0; (xvii)≧16.0; (xviii) ≧17.0; (xix) ≧18.0; (xx) ≧19.0; (xxi) ≧20.0; (xxii)≧25.0; (xxiii) ≧30.0; (xxiv) ≧35.0; (xxv) ≧40.0; (xxvi) ≧45.0; (xxvii)≧50.0; (xxviii) ≧55.0; (xxix) ≧60.0; (xxx) ≧65.0; and (xxxi) ≧70.0. 3.(canceled)
 4. Apparatus as claimed in claim 1, wherein said firstchamber comprises a housing having an ion inlet aperture and a first gasoutlet.
 5. Apparatus as claimed in claim 1, further comprising aninter-chamber aperture connecting said first chamber and said secondchamber.
 6. Apparatus as claimed in claim 1, wherein said first gas ormixture of gases comprises one or more gases selected from the groupconsisting of: (i) helium; (ii) hydrogen; (iii) neon; (iv) methane; (v)ammonia; (vi) nitrogen; (vii) argon; (viii) xenon; (ix) air; and (x) SF6or sulphur hexafluoride. 7-11. (canceled)
 12. Apparatus as claimed inclaim 1, wherein said ion guide comprises: (i) a multipole rod set or asegmented multipole rod set; (ii) an ion tunnel or ion funnel; or (iii)a stack or array of planar, plate or mesh electrodes. 13-26. (canceled)27. Apparatus as claimed in claim 1, wherein said ion guide is arrangedand adapted to receive a beam of ions and to convert or partition saidbeam of ions such that at least one separate group or packets of ions isconfined and/or isolated in said ion guide at any particular time, andwherein each group or packet of ions is separately confined and/orisolated in a separate axial potential well formed in said ion guide.28-30. (canceled)
 31. Apparatus as claimed in claim 1, wherein saidsecond chamber comprises a housing having a second gas outlet and an ionexit aperture.
 32. Apparatus as claimed in claim 1, wherein said secondgas or mixture of gases comprises one or more gases selected from thegroup consisting of: (i) helium; (ii) hydrogen; (iii) neon; (iv)methane; (v) ammonia; (vi) nitrogen; (vii) argon; (viii) xenon; (ix)air; and (x) SF6 or sulphur hexafluoride. 33-35. (canceled) 36.Apparatus as claimed in claim 1, wherein said ion mobility spectrometeror separator comprises a gas phase electrophoresis device. 37-55.(canceled)
 56. Apparatus as claimed in claim 1, further comprising avacuum chamber which houses said first chamber and said second chamber,said vacuum chamber comprising an entrance differential pumpingaperture, an exit differential pumping aperture and a port connected toa vacuum pump.
 57. Apparatus as claimed in claim 56, further comprisingone or more ion guides arranged between said entrance differentialpumping aperture and said first chamber and/or between said secondchamber and said exit differential pumping aperture. 58-60. (canceled)61. A mass spectrometer comprising apparatus as claimed in claim 1.62-67. (canceled)
 68. A method comprising: providing a first chamber;providing a second chamber located downstream of said first chamber;providing an ion guide comprising a plurality of electrodes located insaid first chamber; providing an ion mobility spectrometer or separatorlocated in said second chamber; providing a first gas or mixture ofgases to said first chamber, said first gas or mixture of gases having afirst average density or molecular weight M₁; and providing a second gasor mixture of gases to said second chamber, said second gas or mixtureof gases having a second average density or molecular weight M₂, whereinM₁<M₂.
 69. A method of mass spectrometry comprising a method as claimedin claim
 68. 70-73. (canceled)
 74. A method as claimed in claim 68,wherein the first and second chambers are maintained at substantiallythe same pressure.